The broad objective of the proposed project is to explore the regulatory mechanisms involved in normal cell differentiation and in the malignant change, particularly the reversible suppression in mouse melanoma cells in culture of malignancy and of melanogenesis by low concentrations of 5-bromodeoxyuridine (BrdU). This thymidine analog must be incorporated into the DNA of actively dividing cells in order to cause the many alterations which rapidly occur. Among the changes being studied in BrdU-grown cells are changes at the cell surface, involving increases in measurable quantities of Gross cell surface and histocompatibality antigens, induction of C-type virus and increased immunogenicity. Cells continue to divide at close to normal rate, continue normal rate of DNA, RNA and protein synthesis. During the first 7 days of growth in 3 micron g/ml of BrdU cells progressively stop producing tyrosine and melanin. Tumorigenicity is also markedly reduced. Both differentiated function and tumorigenicity return if the cells are allowed to divide in medium devoid of BrdU showing that the alterations are not true mutations. The mechanism of the BrdU-induced phenomena is being investigated hoping to derive therefrom a better understanding of the controlling signals that are distorted in transmission or reception during the pathology of the neoplastic change.